Delivery of hydroxy carboxylic acids

ABSTRACT

The present invention provides greater than 99% pure bis(triorganosilyl)hydroxycarboxylates of the general formulae: 
     
       
         R 3 SiO—CHR 1 —COO—SiR 3   
       
     
     
       
         R 3 SiO—CHR 1 —R 2 COO—SiR 3   
       
     
     wherein each R is independently a monovalent straight or branched chain alkyl or alkenyl group having from 1 to about 6 carbon atoms, or an aryl group, R 1  may be hydrogen, a monovalent straight or branched chain alkyl group having from 1 to about 18 carbon atoms, or an aryl group, and R 2  is a divalent straight or branched chain alkyl group having from 1 to about 18 carbon atoms, an aryl group, or a straight or branched chain alkaryl group having from 7 to about 18 carbon atoms; a process for producing the bis(trimethylsilyl)hydroxycarboxylates comprising the trimethylsilylation with hexamethyldisilazane of the corresponding hydroxy carboxylic acids; cosmetic formulation comprising the greater than 99% pure bis(trimethylsilyl)hydroxycarboxylates dissolved in aprotic media; and a method of delivering hydroxycarboxylic acids to the epidermis without apparent irritation or inflammation of the epidermis or stratum corneum.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a divisional of application Ser. No. 09/148,675, filed Sep. 4,1998, now allowed 6,143,309, which in turn is a continuation-in-part ofapplication Ser. No. 09/041,173, filed Mar. 12, 1998, now abandoned.

FIELD OF THE INVENTION

The present invention relates to high purity bis(triorganosilyl)hydroxycarboxylic acid derivatives and a method fortheir preparation. More specifically, the present invention relates tomore than 99% pure bis (triorganosilyl)hydroxycarboxylic acidderivatives prepared by triorganosilylation of hydroxycarboxylic acidsby hexaorganodisilazanes. The present invention also relates tonon-irritating cosmetic formulations comprising bis(triorganosilyl)hydroxycarboxylic acid derivatives.

BACKGROUND OF THE PRESENT INVENTION

There is considerable prior art relating to the use of hydroxycarboxylicacids, in particular alphahydroxycarboxylic acids such as glycolic acidand lactic acid, in skin care applications. Alpha-hydroxycarboxylicacids are basically used as chemical versions of facial scrubs. Whenapplied topically, they accelerate the sloughing off of dead cells fromthe outer layer of the skin, the stratum corneum, forcing the underlyingcells in the epidermis to accelerate the creation of fresh new cells toreplace them. The body may also attempt to repair this minor damage, bydepositing new collagen in the underlying dermal layer. The net apparentresult is smoother, firmer, more evenly pigmented skin reminiscent ofthe person's skin at an earlier time chronologically. See generally, webpage found athttp://www.thriveonline.com/@@62AH9wYA2@Hgbb2a/thrive/health/skinsave.intro.htmi(Jul. 9, 1997 11:29 AM).

There are known side effects associated with the use, and in particularthe prolonged use, of alpha-hydroxycarboxylic acids. These include acuteskin irritation on application of the alpha-hydroxycarboxylic acid withpossible development over time of an allergic-like reaction to suchapplications with some patients, and increased sun sensitivity.

Various techniques have been employed to decrease the side effects ofalpha-hydroxycarboxylic acids such as partial neutralization, whichincreases the pH of the applied product (see Market View, The U.S.Cosmetics Industry, “Special Report, AHA Consumer Products 1990-1993,”p.6.); partial or complete esterification, which also increases the pHof the applied product (see Genetic Engineering News dated Apr. 1, 1996found athttp://www.dc.enews.com/magazines/geng_news/archive/960401-005.html onJul. 9, 1997); or the use of additives (see, Hahn, “A New Line ofDefense Against Aging: Breaking the Irritation Barrier,” DCI, January1998). See also, generally, Parab, U.S. Pat. No. 5,420,105; Habif etal., U.S. Pat. No. 5,690,947; Hahn et al., U.S. Pat. No. 5,716,625; DeLacharriere et al., U.S. Pat. No. 5,714,155. None of these approacheschange the real interaction of the alpha-hydroxycarboxylic acid with theepidermis. Rather, they provide the appearance of irritation reduction.

None of the current “solutions” to the irritation problem ofalpha-hydroxycarboxylic acids has approached the problem by changing thedelivery mechanism of the active ingredient such that it does notirritate the outer layers of the skin, yet the active ingredient targetsthe lipid-rich layers of the skin, more efficiently delivering freealpha-hydroxy-carboxylic acid to those sites in the epidermis where thenew cells are created.

Alpha-hydroxycarboxylic acid derivatives which have the ability toefficiently deliver free alpha-hydroxycarboxylic acids to preferredsites in the epidermis to promote new cell and collagen growth withoutirritation of the skin and with no associated toxicity concerns haveclearly been sought for years to no avail. Associated with such amaterial would also be the desire for a simple high yield manufacturingprocess to make the material in the very high purity normally associatedwith cosmetic ingredients.

BRIEF DESCRIPTION OF THE DRAWINGS

The file of this patent contains at least one drawing executed in color.Copies of this patent with color drawing(s) will be provided by thePatent and Trademark Office upon request and payment of the necessaryfee.

FIG. 1 is a colored graphical depiction which shows the results ofapplying a lotion of the present invention in accordance with Example 7to a 36 year old female patient who participated in the study of Example7.

SUMMARY OF THE INVENTION

The present invention provides greater than 99% purebis(triorganosilyl)hydroxy carboxylic acid derivatives of the generalformulae:

R₃SiO—CHR¹—COO-SiR₃

R₃SiO—CHR¹—R²COO—SiR₃

wherein each R is independently a monovalent straight or branched chainalkyl or alkenyl group having from 1 to about 6 carbon atoms, or an arylgroup, R may be hydrogen, a monovalent straight or branched chain alkylgroup having from 1 to about 18 carbon atoms, or an aryl group, and R²is a divalent straight or branched chain alkyl group having from 1 toabout 18 carbon atoms, an aryl group, or a straight or branched chainalkaryl group having from 7 to about 18 carbon atoms. The yield ofbis(triorganosilyl)hydroxy carboxylic acid derivatives prepared by themethod of the present invention is greater than about 95%.

The present invention also provides a simple method for rapidlyproducing bis(triorganosilyl)hydroxycarboxylic acid derivatives of thegeneral formulae:

R₃SiO—CHR¹—COO—SiR₃

R₃SiO—CHR¹—R²COO—SiR₃

wherein each R is independently a monovalent straight or branched chainalkyl or alkenyl group having from 1 to about 6 carbon atoms, or an arylgroup, R¹ may be hydrogen, a monovalent straight or branched chain alkylgroup having from 1 to about 18 carbon atoms, or an aryl group, and R²is a divalent straight or branched chain alkyl group having from 1 toabout 18 carbon atoms, an aryl group, or a straight or branched chainalkaryl group having from 7 to about 18 carbon atoms, the methodcomprising triorganosilylation with a hexaorganodisilazane of thecorresponding hydroxy carboxylic acids of the general formulae:

HO—CHR¹—COOH

HO—CHR¹—R²COOH

wherein R¹ may be hydrogen, a monovalent straight or branched chainalkyl group having from 1 to about 18 carbon atoms, or an aryl group,and R² is a divalent straight or branched chain alkyl group having from1 to about 18 carbon atoms, an aryl group, or a straight or branchedchain alkaryl group having from 7 to about 18 carbon atoms.

It has been found that bis(triorganosilyl)hydroxy-carboxylate materials,which are aprotic, can be readily dissolved in typical aprotic solventsincluding organosilicone materials and can be delivered to the skin evenunder repeat insult conditions with no apparent irritation even underchronic use.

It is well known to those skilled in the art, that organosiliconchemicals containing silylether, Si—O—C, linkages and silylester,Si—O—C═O, linkages are hydrolytically unstable. In particular,silylester linkages are known to those skilled in the art to be morehydrolytically unstable than silylethers. Accordingly,bis(triorganosilyl)hydroxycarboxylates, on exposure to moisture, willundergo hydrolysis forming initially triorganosilylhydroxycarboxylicacids as per Equation 1.

R₃SiOCHR¹COOSiR₃+H2O→R₃SiOCHR¹COOH+R₃SiOH  (1)

Hydrolysis of both silylethers and silylesters is catalyzed by eitheracids or bases, thus although bis(triorganosilyl)hydroxy carboxylatesare neutral, as they begin to hydrolyze they form carboxyiic acids whichcatalyze further hydrolysis. Thus, the hydrolysis process isauto-catalytic. The second step of the hydrolysis process liberates freehydroxycarboxylic acid as per Equation 2.

R₃SiOCHR¹COOH+H2O→HOCHR¹COOH+R₃SiOH  (2)

Bis(triorganosilyl)hydroxycarboxylates of the general formulae:

R₃SiO—CHR¹—COO—SiR₃

R₃SiO—CHR¹—R²COO—SiR₃

wherein each R is independently a monovalent straight or branched chainalkyl or alkenyl group having from 1 to about 6 carbon atoms, or an aryigroup, R¹ may be hydrogen, a monovalent straight or branched chain alkylgroup having from 1 to about 18 carbon atoms, or an aryl group, and R²is a divalent straight or branched chain alkyl group having from 1 toabout 18 carbon atoms, an aryl group, or a straight or branched chainalkaryl group having from 7 to about 18 carbon atoms, have the abilityto deliver hydroxycarboxylic acids to the skin in such a manner as tonot cause irritation or inflammation either acutely or chronically.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides greater than 99% purebis(triorganosilyl)hydroxycarboxylic acid derivatives of the generalformulae:

R₃SiO—CHR¹—COO—SiR₃

R₃SiO—CHR¹—R²COO—SiR₃

wherein each R is independently a monovalent straight or branched chainalkyl or alkenyl group having from 1 to about 6 carbon atoms, or an arylgroup, R¹ may be hydrogen, a monovalent straight or branched chain alkylgroup having from 1 to about 18 carbon atoms, or an aryl group, and R²is a divalent straight or branched chain alkyl group having from 1 toabout 18 carbon atoms, an aryl group, or a straight or branched chainalkaryl group having from 7 to about 18 carbon atoms.

The bis(triorganosilyl)hydroxy carboxylic acid derivatives of thepresent invention are prepared by triorganosilylation with ahexaorganodisilazane of the corresponding hydroxy carboxylic acids ofthe general formulae:

HO—CHR¹—COOH

HO—CHR¹—R²COOH

wherein R¹ may be hydrogen, a monovalent straight or branched chainalkyl group having from 1 to about 18 carbon atoms, or an aryl group,and R² is a divalent straight or branched chain alkyl group having from1 to about 18 carbon atoms, an aryl group, or a straight or branchedchain alkaryl group having from 7 to about 18 carbon atoms.

Hydroxycarboxylic acids suitable for use in the process of the presentinvention, and methods for their preparation are well known to thoseskilled in the art. Specific examples include, but are not limited to,alpha-hydroxycarboxylic acids including glycolic acid and lactic acid,and beta-hydroxy- carboxylic acids including salicylic acid. Thepreferred hydroxy carboxylic acid is lactic acid.

Hexaorganodisilazanes suitable for use in the process of the presentinvention, and methods for their preparation are well known to thoseskilled in the art. Specific examples include, but are not limited tohexamethyldisilazane, hexaethyldisilazane,1,3-divinyltetramethyldisilazane, and 1,3-diethyltetramethyldisilazane.The preferred hexaorganodisilazane is hexamethyldisilazane.

The triorganosilylation reaction may be carried out at temperaturesranging from about 40° C. to about 125° C., preferably between about 60°C. and about 95° C.

The compositions of the present invention are useful for all knownutilities for topical administration of hydroxycarboxylic acids such asα-hydroxy acids and β-hydroxy acids. These include, for example,treatment of dry skin, xerosis, ichthyosis, dandruff, acne, keratoses,psoriasis, wrinkles, warts, blemished skin, hyperpigmented skin,inflammatory dermatoses, eczema, pruritis, hyperkerotic skin,lentigines, melasma, age spots, laxity, leathery texture, roughness,sallow complexion, scaling, telangiectasia, mottled pigmentation, skinatrophy caused by steroids and skin changes associated with intrinsicaging and photodamage.

In addition to the compositions of the present invention, the cosmeticformulations of the present invention may contain any of a large numberof additional cosmetic and pharmaceutical agents, provided that suchadditional agents are inert with respect to formation, stability andactivity of the compositions of the present invention, i.e., they arereaction inert. Additionally any such additives must be aprotic.

Cosmetic and pharmaceutical agents useful in the practice of the presentinvention include those that improve or eradicate age spots, keratosesand wrinkles, analgesics, anesthetics, antiacne agents, antibacterials,antiyeast agents, antifungal agents, antiviral agents, antidandruffagents, antidermatitis agents, antipruritic agents, antiinflammatoryagents, antihyperkeratolytic agents, antidryskin agents,antiperspirants, antipsoriatic agents, antiseborrheic agents, hairconditioners, hair treatment agents, antiaging and antiwrinkile agents,antiphotoaging agents, antiasthmatic agents and bronchodilators,sunscreen agents, antihistamine agents, skin lightening agents,depigmenting agents, vitamins, corticosteroids, tanning agents,hormones, retinoids and topical cardiovascular agents.

The cosmetic formulation may be in the form that any aprotic formulationmay take, including but not limited to lotions, creams, gels, sticks,ointments, liposomes, aerosols, polymeric gels, plasters, patches, filmsor tapes, the preparation of which are well known to those skilled inthe art.

A neat bis(triorganosilyl)lactate can be applied to the skin withsignificantly less injury to the stratum corneum and epidermis thanapplication of lactic acid at a similar aqueous concentration. Solutionsof bis(triorganosilyl)lactate in aprotic vehicles at 10% effectivelactic acid concentration (after hydrolysis), in the form of lotions orointments, can be applied to the skin with no apparent acute or chronicirritation or inflammation.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following examples illustrate the present invention. They are not tobe construed to limit the scope of the appended claims in any mannerwhatsoever.

EXAMPLE 1

In a 3 litre 3-neck RB flask equipped with a magnetic stirring bar, athermometer well and thermometer, addition funnel and heating mantle wasplaced 510 g (4.72 mole) of a 1:1 molar ratio of 83% wt/wt lactic acidin water. This liquid was heated and stirred to 60° C. To the additionfunnel was added 1811 g (11.24 mole) of hexamethyldisilazane and thesystem was blanketed with a dry nitrogen atmosphere.Hexamethyldisilazane was then added slowly with stirring from theaddition funnel to the lactic acid in water mixture, maintaining thetemperature of the mixture at 60° C. Ammonia was liberated from thereaction medium and allowed to escape from the system through a bubbler.The addition of hexamethyidisilazane was continued overnight. Aftercomplete addition of the hexamethyldisilazane the mixture in the RBflask was heated at 80° C. for 4 more hours to ensure that the reactionhad been driven to completion. A GC analysis of the crude product atthis point showed the presence of three materials, hexamethyldisiloxane,hexamethyidisilazane and bis(trimethylsilyl)lactate in the approximateratio of 35:15:50 respectively. The crude product was then fractionatedproducing 700 g (92% theory) of hexamethyldisiloxane, 95 g of a mixtureof hexamethyldisiloxane and hexamethyldisilazane, 260 g (90% theory) ofunreacted hexamethyldisilazane. At this point the remaining liquid wascooled to room temperature, a full vacuum was applied and the productwas distilled at 1 mm of Hg pressure at a temperature of 40° C. toprovide 1050 g (95% yield) of >99.9% pure (by GC analysis) clear,colorless and odorless bis(trimethylsilyl)lactate, refractive index1.4053 (21° C.) and density 0.896 (21° C.). A GC/MS analysis of thismaterial identified the molecular weight of the chemical to be 234.

EXAMPLE 2

In a 250 ml 3-neck RB flask equipped with a magnetic stirring bar, athermometer well and thermometer, a powder addition funnel and heatingmantle was placed 106 g (0.66 mole) of hexamethyldisilazane. This liquidwas heated and stirred to 60° C. To the powder addition funnel was added45 g (0.59 mole) of solid glycolic acid and the system was blanketedwith a dry nitrogen atmosphere. Solid glycolic acid was then addedslowly with stirring from the addition funnel to thehexamethyldisilazane, maintaining the temperature of the mixture at 60°C. Ammonia was liberated from the reaction medium and allowed to escapefrom the system through a bubbler. The addition was completed in 4hours. After complete addition of the glycolic acid the mixture in theRB flask was heated at 80° C. for 4 more hours to ensure that thereaction had been driven to completion. A GC analysis of the crudeproduct at this point showed the presence of two materials,hexamethyldisilazane and bis(trimethyisilyi)-glycolate in theapproximate ratio of 10:90 respectively. The crude product was thenstripped to remove the excess hexamethyldisilazane leaving the productwhich was distilled at a temperature of 45° C. at a vacuum of 1 mm of Hgto provide 120 g (95% yield) of 100% pure (by GC analysis) clear,colorless and odorless bis(trimethylsilyl)glycolate, refractive index1.4119 (21° C.) and density 0.905 (21° C.). A GC/MS analysis of thismaterial identified the molecular weight of the chemical to be 220.

EXAMPLE 3

In a 250 ml 3-neck RB flask equipped with a magnetic stirring bar, athermometer well and thermometer, a powder addition funnel and heatingmantle was placed 59 g (0.37 mole) of hexamethyldisilazane. This liquidwas heated and stirred to 60° C. To the powder addition funnel was added45 g (0.29 mole) of solid salicylic acid and the system was blanketedwith a dry nitrogen atmosphere. Solid salicylic acid was then addedslowly with stirring from the addition funnel to thehexamethyl-disilazane, maintaining the temperature of the mixture at 60°C. Ammonia was liberated from the reaction medium and allowed to escapefrom the system through a bubbler. The addition was completed in 4hours. After complete addition of the salicylic acid the mixture in theRB flask was heated at 80° C. for 4 more hours to ensure that thereaction had been driven to completion. A GC analysis of the crudeproduct at this point showed the presence of two materials,hexamethyldisilazane and bis(trimethylsilyl)salicylate in theapproximate ratio of 25:75 respectively. The crude product was thenstripped to remove the excess hexamethyldisilazane leaving the productwhich was distilled at a temperature of 78° C. at a vacuum of 1 mm of Hgto provide 77 g (95% yield) of 100% pure (by GC analysis) clear,colorless and odorless bis(trimethylsilyl)salicylate, refractive index1.4788 (21° C.) and density 0.99 (21° C.). A GC/MS analysis of thismaterial identified the molecular weight of the chemical to be 282.

EXAMPLE 4

Primary skin irritation studies in rabbits of undilutedbis(trimethylsilyl)lactate was evaluated by Hill Top Research, Inc.(Project No. 97-8487-21) in compliance with the conditions specified inthe regulation for the enforcement of the Federal Hazardous SubstancesAct (16 C.F.R. § 1500). The test material produced moderate to severeerythema and severe edema (raised more than 1 mm and extending beyondthe area of exposure) when applied to one intact and one abraded skinsite on each of six rabbits. Additional changes noted in the colorationor texture of the skin included purple, light brown, green andgreen-brown discoloration on and extending beyond sites; in-depthblanching on site; blanching on and extending beyond site; and site andareas beyond site coriaceous. The Primary Irritation Index (PII) wasfound to be 7.1 based upon erythema and edema. Evidence of corrosion(in-depth blanching) was noted at an intact and abraded site at the 72hour reading. Undiluted bis(trimethylsilyl)lactate is classified as aprimary irritant but not as a corrosive based upon the response observedfollowing dermal application.

For comparison, a solution of 85% lactic acid in water is classified ascorrosive and causes burns. Suitable protective clothing includes heavyrubber gloves and eye and face protection. (Reference: MSDS from AldrichChemical Company, Inc., P.O. Box 355, Milwaukee, Wis. 53201, USA)

EXAMPLE 5

Facial Sensitivity studies in humans were carried out by Hill TopResearch, Inc. (Project Nos. 97-2809-72 and 100969-72). The studiesfollowed a double-blinded paired comparison design of 10% (w/w) lacticacid in water, 25% bis(trimethylsilyl)lactate) in Phenyl Trimethicone,25% bistrimethylsilyl)glycolate in Phenyl Trimethicone, 20%bis(trimethylsilyl)salicylate in Phenyl Trimethicone, PhenylTrimethicone and water. The objective of the studies was to compare thestinging potential of the three trimethylsilylated hydroxyacidderivatives in an anhydrous delivery vehicle to that of the standardwater-based chemical probe under supervised, time applicationprocedures. Thirty female subjects, prequalified as “stingers” to 10%lactic acid, completed the studies where the test samples were appliedto the nasolabial fold. Only three of the thirty subjects demonstrated amild sting response. There were no adverse events associated with theuse of the test articles.

EXAMPLE 6

Anhydrous lotion and anhydrous ointment formulations have been developedcontaining 25% (w/w) bis(trimethylsilyl)lactate as the active ingredientfor chronic exposure and efficacy testing. This concentrationcorresponds to 10% lactic acid upon exposure of the formulations towater and complete hydrolysis of the bis(trimethylsilyl)lactate.

The compositions of the formulations are as follows:

Lotion: 3-n-Hexylheptamethyltrisiloxane 50% Bis(trimethylsilyl)lactate25% Dimethiconol (HMW) 18% Polybutene 4% Caprylyl Trimethicone 2%Pareth-15 0.5% Fragrance 0.5% Ointment: Bis(trimethylsilyl)lactate 25%C24-28 Alkylmethylsiloxane Wax 24.5% Caprylic/Capric/StearicTriglycerides 25% 3-n-Hexylheptamethyltrisiloxane 20% Caprylic/CapricTriglycerides 3% Caprylyl Trimethicone 2% Fragrance 0.5%

Repeat insult daily topical application to human skin of both the lotionand the ointment was carried out for 30 days (60 applications on theinside of the forearm and on the back of the hand). No acute reactionsto these formulations were observed or felt during this period and noindications of sensitization to the formulations were observed.

EXAMPLE 7

The anhydrous lotion and anhydrous ointment formulations described inExample 6 were utilized in a comprehensive efficacy testing programconducted by Hill Top Research, Inc. A lotion and an ointment containingthe same ingredients as described above, except without the active,bis(trimethylsilyl)lactate were also prepared. An efficacy study of thefour formulations, using over 100 women, of ages ranging from 30 to 60years, was conducted over a 90 day period. The group was divided intoapproximately 35 with the active lotion, 17 with the inactive lotion, 35with the active ointment and 17 with the inactive ointment. Participantswere requested to apply their test material to the face twice daily.Visual analysis of participants was conducted at the beginning, andweeks 2, 4, 8 and 12. A trained dermatologist supervised these analyses.Silicone negative facial skin replicates were made of all participantsat the beginning, and weeks 4 and 12. Quantitative analysis of the skinreplicates was obtained by laser light scanning directed at a 25° anglefrom the plane of the replica. A Cohu Solid State B&W camera was used tophotograph each of the scans. The B&W luminance pattern of each scan wasthen converted into a visible color image of each replica. Changes inthe skin surface during the 90 day efficacy test are readily seen viathese color images. Standard statistical methods were used to analyzeall of the data obtained in this study.

Twenty nine within treatment study parameters and fifteen betweentreatment study parameters were determined to be statisticallysignificant. These include reductions in fine lines, coarse wrinkling,mean spacing of lines, tactile roughness, mottled pigmentation,yellowing, and erythema. Reduction in the % of the negative skinreplicate area covered by shadows was statistically significant. Table Ilists all of the study parameters which were identified to haveundergone statistically significant change. FIG. 1 shows the results incolor of one of the 36 year old female patients treated with a lotionwith the active ingredient.

TABLE I Statistically Significant Study Parameter Changes StudyParameter (Within Treatment) % Area Covered by Shadow Cream w/Active vs.Baseline at Week 4 % Area Covered by Shadow Gel w/Active vs. Baseline atWeek 12 Fine Lines Cream Base vs. Baseline at Weeks 2/8 Fine Lines Creamw/Active vs. Baseline at Weeks 2/4/8/12 Fine Lines Gel Base vs. Baselineat Week 8 Fine Lines Gel w/Active vs. Baseline at Weeks 2/4/8/12 CoarseWrinkling Cream w/Active vs. Baseline at Weeks 2/8/12 Coarse WrinklingGel w/Active vs. Baseline at Weeks 2/8 Normal A Roughness Cream w/Activevs. Baseline at Weeks 4/12 Normal A Roughness Gel w/Active vs. Baselineat Weeks 4/12 Normal Z Roughness Cream w/Active vs. Baseline at Weeks4/12 Normal Z Roughness Gel w/Active vs. Baseline at Weeks 4/12 TactileRoughness Cream Base vs. Baseline at Week 8 Tactile Roughness Creamw/Active vs. Baseline at Week 8 Tactile Roughness Gel Base vs. Baselineat Week 8 Tactile Roughness Gel w/Active vs. Baseline at Week 8 ErythemaCream Base vs. Baseline at Weeks 2/4/8/12 Erythema Cream w/Active vs.Baseline at Weeks 2/4/8/12 Mottled Pigmentation Cream Base vs. Baselineat Weeks 2/4/8/12 Mottled Pigmentation Cream w/Active vs. Baseline atWeeks 2/4/8/12 Mottled Pigmentation Gel Base vs. Baseline at Weeks2/4/8/12 Mottled Pigmentation Gel w/Active vs. Baseline at Weeks2/4/8/12 Yellowing Cream Base vs. Baseline at Weeks 2/4/8/12 YellowingCream w/Active vs. Baseline at Weeks 2/4/8/12 Yellowing Gel Base vs.Baseline at Weeks 2/4/8/12 Yellowing Gel w/Active vs. Baseline at Weeks2/4/8/12 Stinging Cream w/Active vs. Baseline at Week 2 only StingingGel w/Active vs. Baseline at Week 2 only Study Parameter (BetweenTreatments) % Area Covered by Shadow Cream w/Active vs. Cream Base FineLines Cream w/Active vs. Cream Base at Weeks 8/12 Fine Lines Gelw/Active vs. Gel Base at Weeks 8/12 Coarse Wrinkling Cream w/Active vs.Cream Base at Weeks 8/12 Coarse Wrinkling Gel w/Active vs. Gel BaseOverall Coarse Wrinkling Cream w/Active vs. Gel w/Active Overall MeanWrinkle Spacing Gel w/Active vs. Gel Base at Week 4 Tactile RoughnessCream w/Active vs. Cream Base Overall Tactile Roughness Gel w/Active vs.Gel Base Overall Erythema Cream w/Active vs. Cream Base Overall ErythemaGel w/Active vs. Gel Base Overall Mottled Pigmentation Cream w/Activevs. Gel w/Active Overall Yellowing Cream w/Active vs. Cream Base OverallYellowing Gel w/Active vs. Gel Base Overall Stinging Gel w/Active vs.Gel Base at Week 2 only

Variations of the present invention will suggest themselves to thoseskilled in the art in light of the above detailed description. Forexample, a mixture of hydroxy carboxylic acids could betriorganosilylated to produce a mixture of Bis(triorganosilyl)hydroxycarboxylic acid derivatives. Similarly, a mixtureof hexaorganodisilazanes can be used to produce a mixture ofbis(triorganosilyl)hydroxycarboxylic acid derivatives. All suchmodifications are within the full intended scope of the appended claims.

All of the above-referenced patents and publications are herebyincorporated by reference.

What is claimed is:
 1. A process for the preparation of greater than 99%pure bis(triorganosilyl)hydroxycarboxylates, said process comprisingreacting free hydroxycarboxylic acids or their hydrates withhexaorganodisilazanes.
 2. A process as defined in claim 1 wherein saidhydroxycarboxylic acid is selected from those of the general formulae:HO—CHR¹—COOH HO—CHR¹—R²COOH wherein R¹ is hydrogen, a monovalentstraight or branched chain alkyl group having from 1 to about 18 carbonatoms, or an aryl group, and R² is a divalent straight or branched chainalkyl group having from 1 to about 18 carbon atoms, an aryl group, or astraight or branched chain alkaryl group having from 7 to about 18carbon atoms.
 3. A process as defined in claim 1 wherein saidhexaorganodisilazane is selected from those of the general formula:R₃SiNHSiR₃ wherein each R is independently a monovalent straight orbranched chain alkyl or alkenyl group having from 1 to about 6 carbonatoms, or an aryl group.
 4. A process as defined in claim 1 wherein thebis(triorganosilyl)hydroxycarboxylate, with a purity in excess of 99%,has the general formulae: R₃SiO—CHR¹—COO—SiR₃ R₃SiO—CHR¹—R²COO—SiR₃wherein each R is independently a monovalent straight or branched chainalkyl or alkenyl group having from 1 to about 6 carbon atoms, or an arylgroup, R¹ is hydrogen, a monovalent straight or branched chain alkylgroup having from 1 to about 18 carbon atoms, or an aryl group, and R²is a divalent straight or branched chain alkyl group having from 1 toabout 18 carbon atoms, an aryl group, or a straight or branched chainalkaryl group having from 7 to about 18 carbon atoms, the processcomprising triorganosilylation with a hexaorganodisilazane selected fromthose of the general formula: R₃SiNHSiR₃ wherein each R is independentlya monovalent straight or branched chain alkyl or alkenyl group havingfrom 1 to about 6 carbon atoms, or an aryl group, of the correspondinghydroxycarboxylic acid of the general formulae: HO—CHR¹—COOHHO—CHR¹—R²COOH wherein R¹ is hydrogen, a monovalent straight or branchedchain alkyl group having from 1 to about 18 carbon atoms, or an arylgroup, and R² is a divalent straight or branched chain alkyl grouphaving from 1 to about 18 carbon atoms, an aryl group, or a straight orbranched chain alkaryl group having from 7 to about 18 carbon atoms. 5.A process as defined in claim 2 wherein the hydroxycarboxylic acid isselected from the group consisting of glycolic acid, lactic acid,salicylic acid and mixtures of any of the foregoing.
 6. A process asdefined in claim 3 wherein the hexaorganodisilazane is selected from thegroup consisting of hexamethyldisilazane,1,3-diethyltetramethyldisilazane, 1,3-divinyltetramethyldisilazane,hexaethyldisilazane and mixtures of any of the foregoing.
 7. Acomposition comprising greater than 99% purebis(triorganosilyl)hydroxycarboxylates produced by the process asdefined in claim
 1. 8. A composition as defined in claim 7 comprisinggreater than 99% pure bis(triorganosilyl)hydroxycarboxylates of thegeneral formulae: R₃SiO—CHR¹—COO—SiR₃ R₃SiO—CHR¹—R²COO—SiR₃ wherein eachR is independently a monovalent straight or branched chain alkyl oralkenyl group having from 1 to about 6 carbon atoms, or an aryl group,R¹ is hydrogen, a monovalent straight or branched chain alkyl grouphaving from 1 to about 18 carbon atoms, or an aryl group, and R² is adivalent straight or branched chain alkyl group having from 1 to about18 carbon atoms, an aryl group, or a straight or branched chain alkarylgroup having from 7 to about 18 carbon atoms.
 9. A composition asdefined in claim 8 comprising greater than 99% purebis(trimethylsilyl)lactate, bis(trimethylsilyl)glycolate,bis(trimethylsilyl)salicylate or mixtures of any of the foregoing.